Method for the preparation of n-(5-nitro-2-furfurylidene)-3-amino-2-oxazolidone



METHOD FOR THE PREPARATION OF N-(S- NITRO-2-FURFURYLIDENE)-3-AMINO -2-OX- AZOLIDONE Gordon D. Drake, Norwich, Gabriel Gever, Oxford, andKenyon J. Hayes, Norwich, N. Y., assignors, by mesne assignments, to TheNorwich Pharmacal Company, Norwich, N. Y., a corporation of New York NoDrawing. Application August 10, 1953, Serial No. 373,437

2 Claims. 01. 260-440) This invention relates to an improved method forthe preparation of N (-nitro-2-furfurylidene)-3-amino-2- oxazolidone, ahighly eflective chemotherapeutic agent in the treatment of microbialinfections.

Various methods for preparingN-(S-nitro-Z-furfurylidene)-3-amino-2-oxazolidone and related compoundshave been set forth in pending applications Serial Nos. 274,066 and274,067, filed February 28, 1952, upon which U. S. Patents Nos.2,749,462 and 2,652,402 have issued, respectively, and owned by theassignee of this application. One of the methods revealed in theaforementioned applications depends upon the reaction of ahydrazinealcohol with an alkyl carbonate, preferably diethyl carbonate,in the presence of an alkaline metal catalyst, preferably sodiummethylate, to yield 3-amino-2-oxazolidone or a substituted3-amino-2-oxazolidone which, upon condensation with5-nitro-2-furaldehyde or a suitable derivative thereof, produces thedesired N-(5-nitro-2-furfurylidene 3-amino-2-oxazolidone.

We have discovered that a considerable improvement in over-all yield ofthe desired product, N-(5-nitro-2-furfurylidene)-3-amino-2-oxazolidonecan be effected if N- (benzylidene)-3-amino-2-oxazolidone prepared inaccordance with the method described in our co-pending applicationSerial No. 374,146, filed August 15, 1953, upon which U. S. Patent No.2,740,792 has issued, is reacted with 5-nitro-2-furaldehyde or suitablederivative thereof in aqueous mineral acid, e. g., sulfuric acid. Thereaction scheme may be represented by the equation set forth below:

O CQHICHO 2CHxCOOH HaCH;

nited States Patent 0" 2,759,931 Patented Aug. 21, 1956 The reactiondepicted by the equation above, whereinN-(benzylidene)-3-amino-2-oxazolidone is caused to react with5-nitro-2-furaldehyde diacetate in an aqueous mineral acid medium suchas dilute sulfuric acid, is carried out in such a fashion that thehydrolysis of benzaldehyde, the steam distillation thereof and thehydrolysis of S-nitro-Z-furaldehyde diacetate to give up the freealdehyde permitting condensation in the reaction medium with3-amino-2-oxazolidone resulting from the hydrolysis ofN-(benzylidene)-3-amino-2-oxazolidone to yield the desired N (5nitro-2-furfurylidene)-3-amino-2 oxazolidone are simultaneouslyeffected. The yield of the N (5nitro-2-furfurylidene)-3-amino-2-oxazolidone is about 92%.

In order that this invention may be fully available to those skilled inthe art, the following illustrative example is given:

EXAMPLE Preparation of N (5-nitr0-2-furfurylidene)-3-amin0-2-oxazolidone In 212 cc. of water are mixed 21.2 grams (0.112 mols) ofN-(benzylidene)-3-amino-2-oxazolidone, 8.93 grams of concentratedsulfuric acid, and 30.1 grams (0.124 mols) of 5-nitro-2-fura1dehydediacetate. This mixture is heated to efiect the hydrolysis ofN-(benzylidene)-3-ami.no- 2-oxazolidone, steam distillation of thebenzaldehyde and hydrolysis of S-nitrQ-Z-furaldehyde diacetate.Approximately 1 /2 hours are required for this reaction to take place.When the bulk of the benzaldehyde has been removed, cc. of 99%isopropanol are added, the reaction mixture is refluxed a short time,and the crystals of N- (5-nitro-2-furfurylidene)-3-amino-2-oxazolidoneare filtered from the hot suspension. The product is washed With waterand isopropanol and dried; a yield of 23.3 grams, 92.8% based onN-(benzylidene)-3-amino-2- oxazolidone of M. P. 254-256" C. is obtained.

What is claimed is:

l. The method of preparingN-(S-nitro-Z-furfurylidene)-3-amino-2-oxazolidone, which compriseshydrolyzing-S-nitro-2-furaldehyde diacetate to produce 5-nitro-2-furaldehyde and causing N-(benzylidene)-3-amino-2- oxazolidone toreact with said 5-nitro-2-furaldehyde in the presence of a dilutemineral acid and under the influence of heat.

2. The method of preparing N-(S-nitro-Z-furfurylidene)-3-amino-2-oxazolidone, which comprises mixing N(benzylidene)-3-amino-2-oxazolidone with 5-nitro- Z-furaldehydediacetate and sulfuric acid in water, and applying heat to said mixtureto effect the simultaneous hydrolysis of N (benzylidene)3-amino2-oxazolidone, steam distillation of benzaldehyde, and hydrolysisof 5- nitro-Z-furaldehyde diacetate to liberate free aldehyde and efiectcondensation in the reaction medium with 3-amino- 2-oxazolidoneresulting from the hydrolysis of said N-(benzylidene)-3-amino-2-oxazolidone.

No references cited.

1. THE METHOD OF PREPARINGN-(5-NITRO-2-FURFURYLIDENE)-3-AMINO-2-OXAZOLIDONE, WHICH COMPRISESHYDROLYZING-5-NITRO-2-FURALDEHYDE DIACETATE TO PRODUCE5-NITRO2-FURALDEHYDE AND CAUSING N-(BENZYLIDENE)-3-AMINO-2OXAZOLIDONE TOREACT WITH SAID 5-NITRO-2-FURALDEHYDE IN THE PRESENCE OF A DILUTEMINERAL ACID AND UNDER THE INFLUENCE OF HEAT.